Kapteijns Kirsten C J, van Prooije Teije H, Li Hao, Scheenen Tom W J, Tuladhar Anil Man, van de Warrenburg Bart P
Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Netherlands; Department of Medical Imaging, Radboud University Medical Center, Netherlands.
Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Netherlands.
Neuroimage Clin. 2025;46:103783. doi: 10.1016/j.nicl.2025.103783. Epub 2025 Apr 21.
Spinocerebellar ataxia type 1 (SCA1) is a rare, neurodegenerative disease. Upcoming clinical disease-modifying trials require biomarkers sensitive to disease progression. This study aims to investigate diffusion MRI (dMRI) metrics as a possible outcome measure in such trials.
46 participants (26 SCA1, 20 matched healthy controls (HC)) underwent 3 T MRI examination and clinical assessment of ataxia severity (SARA) at three timepoints over the duration of two years, including dMRI. Diffusion metrics (fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity) were examined using tract-based spatial statistics (TBSS) and ROI-based extraction. Results were evaluated for change over time and relation to disease severity.
Cerebellar white matter, in particular all cerebellar peduncles, showed significant (p < 0.001) differences between SCA1 and HC groups at baseline in all diffusion metrics. After two years, dynamics were only observed in the inferior cerebellar peduncle (ICP). However, a sub-group of early-stage disease patients (SARA ≤ 11) showed significant change in the corticospinal tract (CST) and pontine crossing tract (PCT), indicating stage-dependent dynamics. Cortical regions did not show cross-sectional differences between groups, but did change significantly in both anterior and posterior regions in the SCA1 group (p < 0.001).
SCA1 patients showed significantly impaired white matter integrity in the cerebellar regions, when compared to HC. At the group level, diffusion metrics show dynamic effects in the ICP and in cortical regions. Patients in early disease stages furthermore show dynamic change in the CST and PCT. This indicates that white matter alterations follow a specific pattern throughout the disease and that measurements thereof are most useful in clinical trials targeting early disease stages.
1型脊髓小脑共济失调（SCA1）是一种罕见的神经退行性疾病。即将开展的临床疾病修饰试验需要对疾病进展敏感的生物标志物。本研究旨在探讨扩散磁共振成像（dMRI）指标作为此类试验中可能的结局指标。
46名参与者（26名SCA1患者，20名匹配的健康对照（HC））在两年期间的三个时间点接受了3T磁共振成像检查和共济失调严重程度（SARA）的临床评估，包括dMRI。使用基于纤维束的空间统计学（TBSS）和基于感兴趣区（ROI）的提取方法检查扩散指标（分数各向异性、平均扩散率、径向扩散率、轴向扩散率）。评估结果随时间的变化以及与疾病严重程度的关系。
在所有扩散指标方面，SCA1组和HC组在基线时小脑白质，尤其是所有小脑脚，存在显著差异（p < 0.001）。两年后，仅在小脑下脚（ICP）观察到动态变化。然而，一组早期疾病患者（SARA≤11）的皮质脊髓束（CST）和脑桥交叉束（PCT）出现了显著变化，表明存在阶段依赖性动态变化。皮质区域在组间未显示出横断面差异，但SCA1组的前部和后部区域均有显著变化（p < 0.001）。
与HC相比，SCA1患者小脑区域的白质完整性明显受损。在组水平上，扩散指标在ICP和皮质区域显示出动态效应。疾病早期的患者在CST和PCT中也显示出动态变化。这表明白质改变在整个疾病过程中遵循特定模式，并且对其进行测量在针对疾病早期阶段的临床试验中最为有用。
